POS1535 EARLY IMPROVEMENT IN 3VAS/4VAS PREDICTS REDUCED RATES OF RADIOGRAPHIC CHANGE IN BIO-NAIVE ACTIVE PSORIATIC ARTHRITIS PATIENTS RECEIVING GUSELKUMAB TREATMENT
Authors: W. Tillett, L. Coates, M. Vis, E. Soriano, J. F. Merola, M. Zimmermann, M. Shawi, M. Sharaf, P. Nash, P. Helliwell
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Guselkumab (GUS), a fully human IL-23p19 subunit inhibitor, was shown to reduce mean changes in radiographic progression vs placebo (PBO) by week (W)24 <sup>[1]</sup> and to be associated with low rates of radiographic progression through W100 among GUS-treated patients (pts) with PsA, irrespective of dosing regimen (every [Q] 4W or Q8W) <sup>[2]</sup> Furthermore, earlier clinical response predicted improved long-term radiographic outcome in GUS-treated pts with active PsA <sup>[3]</sup>. The recently developed 3 Visual Analogue Scale (VAS) and 4 VAS scores are the first short multidimensional composite measures specifically for use in PsA routine clinical care <sup>[4]</sup>. <h3>Objectives</h3> Determine whether early improvement in 3VAS/4VAS predicts radiographic change through W100. <h3>Methods</h3> DISCOVER-2 included biologic-naïve pts with active PsA (≥5 swollen and ≥5 tender joint counts [SJC/TJC]; CRP ≥0.6 mg/dL) randomized (1:1:1) to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO with crossover to GUS 100 mg Q4W at W24. In the current analysis, only pts randomized to GUS were included (N=493), pooling Q4W and Q8W. Response at W8 was defined as achievement of low disease activity (LDA) in 3VAS (≤3.4), 4VAS (≤3.5), RAPID3 (≤6), DAPSA (≤14), and PASDAS (≤3.2). Association of W8 response with change from baseline (BL) to W100 in total PsA-modified van der Heijde-Sharp [vdH-S] score was assessed with the independent samples t-test and generalized linear models adjusting for known BL determinants of radiographic progression (vdH-S score, age, gender, and CRP). Pairwise correlations and agreement in LDA classification between the endpoints assessed were assessed with Pearson's correlation coefficient and the kappa statistic, respectively. <h3>Results</h3> Among GUS-treated pts not meeting the respective endpoints at BL, 32.9%, 31.6%, 12.4%, 17.8%, and 10.8% achieved LDA in 3VAS, 4VAS, RAPID3, DAPSA, and PASDAS, respectively, at W8. LDA achievement in 3VAS (0.86 vs. 2.15, p=0.03), RAPID3 LDA (0.74 vs. 1.80, p=0.049), DAPSA LDA (-0.05 vs. 2.08, p&lt;0.001), and PASDAS LDA (0.58 vs. 1.87, p=0.006) at W8 were associated with significantly less radiographic progression through W100 <b>(Figure 1</b>). For 4VAS, achievement of remission (≤2.1; 0.71 vs. 1.84, p=0.045), but not LDA (1.12 vs. 2.01, p=0.142), was also associated with improved radiographic outcome. In multivariate analyses, improved response to GUS treatment at W8 in all endpoints assessed was associated with numerically less radiographic progression through W100. 3VAS and 4VAS at W8 showed strong correlations with RAPID3 (r<sub>3VAS</sub>=0.787; r<sub>4VAS</sub>=0.877) and PASDAS (r<sub>3VAS</sub>=0.795; r<sub>4VAS</sub>=0.790) and moderate correlations with DAPSA (r<sub>3VAS</sub>=0.466; r<sub>4VAS</sub>=0.524), whereas fair to moderate agreement (kappa range: 0.325-0.545) in LDA classification was noted. <h3>Conclusion</h3> Approximately one-third of GUS-treated patients achieved early response (W8 LDA) in 3VAS/4VAS, which was associated with reduced rates of radiographic change, as was early response in the other outcomes assessed. These results suggest that, in addition to their usefulness in assessing disease activity in routine clinical care, 3VAS and 4VAS, the former being more sensitive, may predict long-term radiographic changes. <h3>References</h3> [1]Mease PJ, et al. <i>Lancet.</i> 2020;395:1126–36 [2]McInnes IB, et al. <i>Arthritis Rheumatol.</i> 2022;74:475-85 [3]Mease PJ, et al. <i>Ann Rheum Dis</i>. 2022;81:828-29 [4]Tillett W, et al. <i>J Rheumatol</i>. 2021;jrheum.201675 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> William Tillett Speakers bureau: Abbvie, Amgen, Eli-Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Consultant of: Abbvie, Amgen, Eli-Lilly, Janssen, MSD, Novartis, Ono-Pharma, Pfizer, and UCB, Grant/research support from: Abbvie, Amgen, Eli-Lilly, Janssen, UCB and Pfizer, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Funded by a National Institute for Health Research Clinician Scientist award. The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We acknowledge the support of the National Institute for Health Research Clinical Research Network (NIHR CRN)., Marijn Vis Speakers bureau: Has received research grants, consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB, and the Dutch Arthritis Foundation., Consultant of: Has received research grants, consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB, and the Dutch Arthritis Foundation., Grant/research support from: Has received research grants, consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB, and the Dutch Arthritis Foundation., Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche and UCB, Joseph F. Merola Consultant of: Is a consultant and/or investigator for Amgen, Bristol Myers Squibb, Abbvie, Dermavant, Eli Lilly, Incyte, Novartis, Janssen, UCB, Sanofi, Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma. Payments received are considered honorarium, Miriam Zimmermann Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies, a wholly owned subsidiary of Johnson &amp; Johnson, Mohamed Sharaf Employee of: Janssen MEA, Dubai United Arab Emirates, Peter Nash Speakers bureau: Received grants for research and clinical trials and honoraria for advice and lectures on behalf of: UCB, Abbvie, Pfizer, Lilly, Novartis, GSK, MSD, Samsung, Janssen, Gilead/Galapagos, Boeringher-Ingelheim, Sun, Consultant of: Received grants for research and clinical trials and honoraria for advice and lectures on behalf of: UCB, Abbvie, Pfizer, Lilly, Novartis, GSK, MSD, Samsung, Janssen, Gilead/Galapagos, Boeringher-Ingelheim, Sun, Grant/research support from: Received grants for research and clinical trials and honoraria for advice and lectures on behalf of: UCB, Abbvie, Pfizer, Lilly, Novartis, GSK, MSD, Samsung, Janssen, Gilead/Galapagos, Boeringher-Ingelheim, Sun, Philip Helliwell Speakers bureau: Abbvie, Novartis, Janssen, Consultant of: Eli Lilly.